Banani, S. F., Lee, H. O., Hyman, A. A. & Rosen, M. K. Biomolecular condensates: organizers of cellular biochemistry. Nat. Rev. Mol. Cell Biol. 18, 285–298 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Brangwynne, C. P., Tompa, P. & Pappu, R. V. Polymer physics of intracellular phase transitions. Nat. Phys. 11, 899–904 (2015).

Article  CAS  Google Scholar 

Dignon, G. L., Best, R. B. & Mittal, J. Biomolecular phase separation: from molecular driving forces to macroscopic properties. Annu. Rev. Phys. Chem. 71, 53–75 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Patel, A. et al. A liquid-to-solid phase transition of the ALS protein FUS accelerated by disease mutation. Cell 162, 1066–1077 (2015).

Article  CAS  PubMed  Google Scholar 

Wang, J. et al. A molecular grammar governing the driving forces for phase separation of prion-like RNA binding proteins. Cell 174, 688–699 e16 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Saar, K. L. et al. Learning the molecular grammar of protein condensates from sequence determinants and embeddings. Proc. Natl Acad. Sci. USA 118, e2019053118 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kato, M. & McKnight, S. L. The low-complexity domain of the FUS RNA binding protein self-assembles via the mutually exclusive use of two distinct cross-beta cores. Proc. Natl Acad. Sci. USA 118, e2114412118 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lin, Y. H., Forman-Kay, J. D. & Chan, H. S. Theories for sequence-dependent phase behaviors of biomolecular condensates. Biochemistry 57, 2499–2508 (2018).

Article  CAS  PubMed  Google Scholar 

Mittag, T. & Pappu, R. V. A conceptual framework for understanding phase separation and addressing open questions and challenges. Mol. Cell 82, 2201–2214 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Vendruscolo, M. & Fuxreiter, M. Towards sequence-based principles for protein phase separation predictions. Curr. Opin. Chem. Biol. 75, 102317 (2023).

Article  CAS  PubMed  Google Scholar 

Rubinstein, M. & Dobrynin, A. V. Solutions of associative polymers. Trends Polym. Sci. 5, 181–186 (1997).

CAS  Google Scholar 

Rubinstein, M. & Semenov, A. N. Thermoreversible gelation in solutions of associating polymers. 2. Linear dynamics. Macromolecules 31, 1386–1397 (1998).

Article  CAS  Google Scholar 

Ginell, G. M. & Holehouse, A. S. in Phase-Separated Biomolecular Condensates: Methods and Protocols (eds Zhou, H.-X. et al.) 95–116 (Springer, 2023).

Banjade, S. et al. Conserved interdomain linker promotes phase separation of the multivalent adaptor protein Nck. Proc. Natl Acad. Sci. USA 112, E6426–E6435 (2015).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yang, Y., Jones, H. B., Dao, T. P. & Castaneda, C. A. Single amino acid substitutions in stickers, but not spacers, substantially alter UBQLN2 phase transitions and dense phase material properties. J. Phys. Chem. B 123, 3618–3629 (2019).

Article  CAS  PubMed  Google Scholar 

Dignon, G. L., Zheng, W., Kim, Y. C., Best, R. B. & Mittal, J. Sequence determinants of protein phase behavior from a coarse-grained model. PLoS Comput. Biol. 14, e1005941 (2018).

Article  PubMed  PubMed Central  Google Scholar 

Regy, R. M., Thompson, J., Kim, Y. C. & Mittal, J. Improved coarse-grained model for studying sequence dependent phase separation of disordered proteins. Protein Sci. 30, 1371–1379 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Martin, E. W. et al. Valence and patterning of aromatic residues determine the phase behavior of prion-like domains. Science 367, 694–699 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bremer, A. et al. Deciphering how naturally occurring sequence features impact the phase behaviours of disordered prion-like domains. Nat. Chem. 14, 196–207 (2022).

Article  CAS  PubMed  Google Scholar 

Farag, M. et al. Condensates formed by prion-like low-complexity domains have small-world network structures and interfaces defined by expanded conformations. Nat. Commun. 13, 7722 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Quiroz, F. G. & Chilkoti, A. Sequence heuristics to encode phase behaviour in intrinsically disordered protein polymers. Nat. Mater. 14, 1164–1171 (2015).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mohanty, P. et al. A synergy between site-specific and transient interactions drives the phase separation of a disordered, low-complexity domain. Proc. Natl Acad. Sci. USA 120, e2305625120 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang, S. H., Zheng, T. & Fawzi, N. L. Structure and position-specific interactions of prion-like domains in transcription factor Efg1 phase separation. Biophys. J. 123, 1481–1493 (2024).

Article  CAS  PubMed  Google Scholar 

Murthy, A. C. et al. Molecular interactions underlying liquid–liquid phase separation of the FUS low-complexity domain. Nat. Struct. Mol. Biol. 26, 637–648 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Murthy, A. C. et al. Molecular interactions contributing to FUS SYGQ LC–RGG phase separation and co-partitioning with RNA polymerase II heptads. Nat. Struct. Mol. Biol. 28, 923–935 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Brady, J. P. et al. Structural and hydrodynamic properties of an intrinsically disordered region of a germ cell-specific protein on phase separation. Proc. Natl Acad. Sci. USA 114, E8194–E8203 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rekhi, S. et al. Expanding the molecular language of protein liquid–liquid phase separation. Nat. Chem. 16, 1113–1124 (2024).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Johnson, C. N. et al. Insights into molecular diversity within the FET family: unraveling phase separation of the N-terminal low complexity domain from RNA-binding protein EWS. J. Am. Chem. Soc. 146, 8071–8085 (2024).

Article  CAS  PubMed  Google Scholar 

Flores-Solis, D. et al. Driving forces behind phase separation of the carboxy-terminal domain of RNA polymerase II. Nat. Commun. 14, 5979 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zheng, W. et al. Molecular details of protein condensates probed by microsecond long atomistic simulations. J. Phys. Chem. B 124, 11671–11679 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ranganathan, S., Dasmeh, P., Furniss, S. & Shakhnovich, E. Phosphorylation sites are evolutionary checkpoints against liquid-solid transition in protein condensates. Proc. Natl Acad. Sci. USA 120, e2215828120 (2023).